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Cytoprotective remedies for ameliorating nephrotoxicity induced by renal oxidative stress
Ranmali Ranasinghe1, Michael Mathai1, Anthony Zulli1
1Institute for Health and Sport, College of Health and Medicine, Victoria University, Melbourne, Victoria, Australia.
Aims:
Nephrotoxicity is the hallmark of anti-neoplastic drug metabolism that causes oxidative stress. External chemical agents and prescription drugs release copious amounts of free radicals originating from molecular oxidation and unless sustainably scavenged, they stimulate membrane lipid peroxidation and disruption of the host antioxidant mechanisms. This review aims to provide a comprehensive collection of potential cytoprotective remedies in surmounting the most difficult aspect of cancer therapy as well as preventing renal oxidative stress by other means.
Materials And Methods:
Over 400 published research and review articles spanning several decades were scrutinised to obtain the relevant data which is presented in 3 categories; sources, mechanisms, and mitigation of renal oxidative stress.
Key-Findings:
Drug and chemical-induced nephrotoxicity commonly manifests as chronic or acute kidney disease, nephritis, nephrotic syndrome, and nephrosis. Renal replacement therapy requirements and mortalities from end-stage renal disease are set to rapidly increase in the next decade for which 43 different cytoprotective compounds which have the capability to suppress experimental nephrotoxicity are described.
Significance:
The renal system performs essential homeostatic functions that play a significant role in eliminating toxicants, and its accumulation and recurrence in nephric tissues results in tubular degeneration and subsequent renal impairment. Global statistics of the latest chronic kidney disease prevalence is 13.4 % while the end-stage kidney disease requiring renal replacement therapy is 4-7 million per annum. The remedial compounds discussed herein had proven efficacy against nephrotoxicity manifested consequent to impaired antioxidant mechanisms in preclinical models produced by renal oxidative stress activators.
Insights
This review identifies 43 cytoprotective compounds to combat drug-induced nephrotoxicity and oxidative stress, offering hope for kidney protection during cancer therapy and beyond.
Area of Science:
- Nephrology
- Pharmacology
- Toxicology
Background:
- Anti-neoplastic drugs and chemicals induce nephrotoxicity via oxidative stress, damaging kidney tissues and impairing antioxidant mechanisms.
- Free radicals from molecular oxidation lead to lipid peroxidation and cellular damage, contributing to kidney disease.
- Kidney disease prevalence is rising, with millions annually requiring renal replacement therapy.
Purpose of the Study:
- To review and compile cytoprotective remedies for mitigating cancer therapy-related nephrotoxicity.
- To explore strategies for preventing renal oxidative stress from various chemical agents.
- To provide a comprehensive resource on compounds that counteract drug-induced kidney damage.
Main Methods:
- Systematic review of over 400 research and review articles.
- Data categorized by sources, mechanisms, and mitigation of renal oxidative stress.
- Focus on preclinical models demonstrating efficacy against nephrotoxicity.
Main Results:
- Identified 43 cytoprotective compounds effective in suppressing experimental nephrotoxicity.
- Drug-induced nephrotoxicity manifests as various kidney diseases, including chronic kidney disease and nephrosis.
- Significant increase in end-stage renal disease and renal replacement therapy projected.
Conclusions:
- The kidney's role in detoxification makes it vulnerable to toxicant accumulation and impairment.
- Cytoprotective compounds show proven efficacy in preclinical models against oxidative stress-induced nephrotoxicity.
- These findings offer potential therapeutic avenues for managing and preventing kidney damage.
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